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    • Keywords


      Brown adipose tissue; HP1; Igf2P0; placental development; Upc1

    • Abstract


      Mammals have three HP1 protein isotypes HP1𝛽 (CBX1), HP1𝛾 (CBX3) and HP1𝛼 (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5. Recent work has shown that reduction of CBX3 protein in homozygotes for a hypomorphic allele (Cbx3hypo) causes a severe postnatal mortality with around 99% of the homozygotes dying before weaning. It is not known what the causes of the postnatal mortality are. Here we show that Cbx3hypo/hypo conceptuses are significantly reduced in size and the placentas exhibit a haplo-insufficiency. Late gestation Cbx3hypo/hypo placentas have reduced mRNA transcripts for genes involved in growth regulation, amino acid and glucose transport. Blood vessels within the Cbx3hypo/hypo placental labyrinth are narrower than wild-type. Newborn Cbx3hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves and there is almost complete loss of stored lipid in brown adipose tissue (BAT). There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose product is responsible for non-shivering themogenesis. We suggest that it is the small size of the Cbx3hypo/hypo neonates, a likely consequence of placental growth and transport defects, combined with a possible inability to thermoregulate that causes the severe postnatal mortality.

    • Author Affiliations


      Ebru Aydin1 Dick-Paul Kloos2 Emmanuel Gay2 Willem Jonker2 Lijuan Hu1 Jörn Bullwinkel3 Jeremy P Brown3 4 Maria Manukyan5 Martin Giera2 Prim B Singh3 4 6 Reinald Fundele1

      1. Sub-department of Evolution & Development, Center for Evolutionary Biology, Uppsala University, Norbyvägen 18A, S-75236 Uppsala, Sweden
      2. Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Albinusdreef 2, 2300 RC Leiden, The Netherlands
      3. Division of Immunoepigenetics, Department of Immunology and Cell Biology, Research Center Borstel, D-23845 Borstel, Germany
      4. Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany
      5. Albert-Ludwigs-Universität Freiburg, BIOSS Centre for Biological Signalling Studies, Schänzlestrasse 18, 79104 Freiburg, Germany
      6. School of Natural Sciences and Psychology, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK
    • Dates

  • Journal of Biosciences | News

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      Posted on July 25, 2019

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